Abstract
Uterine Fibroids, or leiomyomata, affect millions of women world-wide, with a high incidence of 75% within women of reproductive age. In ~30% of patients, uterine fibroids cause menorrhagia, or heavy menstrual bleeding, and more than half of the patients experience symptoms such as heavy menstrual bleeding, pelvic pain, or infertility. Treatment is symptomatic with limited options including hysterectomy as the most radical solution. The genetic foundations of uterine fibroid growth have been traced to somatic driver mutations (MED12, HMGA2, FH−/−, and COL4A5-A6). These also lead to downstream expression of angiogenic factors including IGF-1 and IGF-2, as opposed to the VEGF-driven mechanism found in the angiogenesis of hypoxic tumors. The resulting vasculature supplying the fibroid with nutrients and oxygen is highly irregular. Of particular interest is the formation of a pseudocapsule around intramural fibroids, a unique structure within tumor angiogenesis. These aberrations in vascular architecture and network could explain the heavy menstrual bleeding observed. However, other theories have been proposed such as venous trunks, or venous lakes caused by the blocking of normal blood flow by uterine fibroids, or the increased local action of vasoactive growth factors. Here, we review and discuss the evidence for the various hypotheses proposed.
Highlights
HEAVY MENSTRUAL BLEEDING AND UTERINE FIBROIDSAs many as 1 in 20 women aged between 30 and 49 years consult their GP each year because of heavy menstrual bleeding (HMB) or menstrual problems, with menstrual disorders the reason for 12% of all referrals to gynecology services in the UK [1]
Reviewed by: Moamar Al-Jefout, United Arab Emirates University, United Arab Emirates Essam R
These lead to downstream expression of angiogenic factors including insulin-like growth factor (IGF)-1 and IGF-2, as opposed to the vascular endothelial growth factor (VEGF)-driven mechanism found in the angiogenesis of hypoxic tumors
Summary
As many as 1 in 20 women aged between 30 and 49 years consult their GP each year because of heavy menstrual bleeding (HMB) or menstrual problems, with menstrual disorders the reason for 12% of all referrals to gynecology services in the UK [1]. While HMB was historically given as a blood loss of more than 80 mL per day [2]—a definition not considered useful any longer given the large variation in women’s physique and the fact that most women who seek treatment for HMB do not meet this criterion [3]—HMB is defined as “excessive menstrual blood loss which interferes with a woman’s physical, social, emotional and/or material quality of life” [1]. It can occur on its own or in combination with other symptoms such as acute and chronic pelvic pain, or infertility [4]. The potential causes for HMB are many, such as ovulatory disorders, adenomyosis, endometriosis, endometrial polyps, and endometrial hyperplasia [6]; the most common condition underlying HMB are uterine fibroids
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